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Title: Anaplerotic roles of pyruvate carboxylase in mammalian tissues
Authors: S. Jitrapakdee
A. Vidal-Puig
J. C. Wallace
Mahidol University
University of Cambridge
University of Adelaide
Keywords: Biochemistry, Genetics and Molecular Biology
Issue Date: 1-Apr-2006
Citation: Cellular and Molecular Life Sciences. Vol.63, No.7-8 (2006), 843-854
Abstract: Pyruvate carboxylase (PC) catalyzes the ATP-dependent carboxylation of pyruvate to oxaloacetate. PC serves an anaplerotic role for the tricarboxylic acid cycle, when intermediates are removed for different biosynthetic purposes. In liver and kidney, PC provides oxaloacetate for gluconeogenesis. In adipocytes PC is involved in de novo fatty acid synthesis and glyceroneogenesis, and is regulated by the peroxisome proliferator-activated receptor-γ, suggesting that PC is involved in the metabolic switch controlling fuel partitioning toward lipogenesis. In islets, PC is necessary for glucose-induced insulin secretion by providing oxaloacetate to form malate that participates in the 'pyruvate/malate cycle' to shuttle 3C or 4C between mitochondria and cytoplasm. Hyperglycemia and hyperlipidemia impair this cycle and affect glucose-stimulated insulin release. In astrocytes, PC is important for de novo synthesis of glutamate, an important excitatory neurotransmitter supplied to neurons. Transcriptional studies of the PC gene pinpoint some transcription factors that determine tissue-specific expression. © Birkhäuser Verlag, 2006.
ISSN: 15691632
Appears in Collections:Scopus 2006-2010

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